| The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. | |
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MedLine Citation:
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PMID: 23298836 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Fusion genes are chromosomal aberrations that are found in many cancers and can be used as prognostic markers and drug targets in clinical practice. Fusions can lead to production of oncogenic fusion proteins or to enhanced expression of oncogenes. Several recent studies have reported that some fusion genes can escape microRNA regulation via 3'-untranslated region (3'-UTR) deletion. We performed whole transcriptome sequencing to identify fusion genes in glioma and discovered FGFR3-TACC3 fusions in 4 of 48 glioblastoma samples from patients both of mixed European and of Asian descent, but not in any of 43 low-grade glioma samples tested. The fusion, caused by tandem duplication on 4p16.3, led to the loss of the 3'-UTR of FGFR3, blocking gene regulation of miR-99a and enhancing expression of the fusion gene. The fusion gene was mutually exclusive with EGFR, PDGFR, or MET amplification. Using cultured glioblastoma cells and a mouse xenograft model, we found that fusion protein expression promoted cell proliferation and tumor progression, while WT FGFR3 protein was not tumorigenic, even under forced overexpression. These results demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma. |
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Authors:
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Brittany C Parker; Matti J Annala; David E Cogdell; Kirsi J Granberg; Yan Sun; Ping Ji; Xia Li; Joy Gumin; Hong Zheng; Limei Hu; Olli Yli-Harja; Hannu Haapasalo; Tapio Visakorpi; Xiuping Liu; Chang-Gong Liu; Raymond Sawaya; Gregory N Fuller; Kexin Chen; Frederick F Lang; Matti Nykter; Wei Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-09 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 123 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-04-19 Completed Date: 2013-05-13 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 855-65 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3' Untranslated Regions Animals Base Sequence Brain Neoplasms / genetics*, metabolism Chromosomes, Human, Pair 4 / genetics Gene Expression Regulation, Neoplastic Gene Fusion* Glioblastoma / genetics*, metabolism Glioma / genetics, metabolism Humans Male Mice Mice, Nude MicroRNAs / genetics*, metabolism Microtubule-Associated Proteins / genetics*, metabolism Molecular Sequence Data Oncogene Proteins, Fusion / genetics, metabolism RNA, Neoplasm / genetics Receptor, Fibroblast Growth Factor, Type 3 / genetics*, metabolism Tandem Repeat Sequences Transplantation, Heterologous Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA016672/CA/NCI NIH HHS; U24CA143835/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3' Untranslated Regions; 0/MIRN99 microRNA, human; 0/MicroRNAs; 0/Microtubule-Associated Proteins; 0/Oncogene Proteins, Fusion; 0/RNA, Neoplasm; 0/TACC3 protein, human; EC 2.7.10.1/FGFR3 protein, human; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3 |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2013 Feb 1;123(2):548-51
[PMID:
23298839
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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